Ординатура / Офтальмология / Английские материалы / Mechanisms of the Glaucomas_Shields, Tombran-Tink, Barnstable_2008

MECHANISMS OF THE GLAUCOMAS

OPHTHALMOLOGY RESEARCHTM

JOYCE TOMBRAN-TINK, PhD, AND COLIN J. BARNSTABLE, DPhil

SERIES EDITORS

Visual Transduction and Non-Visual Light Perception, edited by Joyce Tombran-Tink, PhD, and Colin J. Barnstable, DPhil, 2008

Mechanisms of the Glaucomas: Disease Processes and Therapeutic Modalities, edited by Joyce Tombran-Tink, PhD, Colin J. Barnstable, DPhil, and M. Bruce Shields, MD, 2008

Visual Prosthesis and Ophthalmic Devices: New Hope in Sight, edited by

Joyce Tombran-Tink, PhD, Colin J. Barnstable, DPhil, and Joseph F. Rizzo, MD, 2007

Retinal Degenerations: Biology, Diagnostics, and Therapeutics, edited by Joyce Tombran-Tink, PhD, and Colin J. Barnstable, DPhil, 2007

Ocular Angiogenesis: Diseases, Mechanisms, and Therapeutics, edited by Joyce Tombran-Tink, PhD, and Colin J. Barnstable, DPhil, 2006

Library of Congress Control Number: 2007940761

©2008 Humana Press, a part of Springer Science+Business Media, LLC

All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, 999 Riverview Drive, Suite 208, Totowa, NJ 07512 USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden.

The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

Cover illustration: Figure 3 and Figure 6, Chapter 7, “Glaucomatous changes in the Trabecular Meshwork,” by Douglas H. Johnson and Elke Lutjen-Drecoll. Photo of optic nerve head provided by M. Bruce Shields.

Printed on acid-free paper

9 8 7 6 5 4 3 2 1

springer.com

Dedicated to the memory of

Douglas H. Johnson, MD

April 17, 1951–July 26, 2007

Who contributed to this book and, as a true clinician-scientist, made major contributions to our understanding of glaucoma

has become an important part of our treatment plan, although the magnitude and duration of intraocular pressure reduction is limited, and a high percentage of patients eventually require the more definitive filtering or drainage implant surgery.

Filtering surgery is truly a product of the twentieth century, having been introduced around 1906. The technique evolved throughout the century, with the transition from full-thickness fistulas to the guarded trabeculectomy, the application of microsurgical techniques, and the adjunctive use of antifibrotic agents. However, the operation is still limited by a significant rate of failures and complications, which prompted the development during the second half of the century of drainage implant devices as an alternative to glaucoma filtering surgery. While both of these commonly used surgical techniques have serious shortcomings—and the quest goes on for better glaucoma operations—they have undoubtedly saved the sight of countless thousands of patients with glaucoma.

So, what was the greatest contribution to glaucoma in the twentieth century? Was it the ability to accurately measure the intraocular pressure or to document the extent of the visual field loss or to analyze the status of the optic nerve head? Or, was it the dramatic advances in glaucoma pharmacology or the application of laser technology or the incisional surgical procedures, when the former treatments were ineffective? While all of these diagnostic and therapeutic advances have undoubtedly been critical in the prevention of blindness from glaucoma, a careful analysis of the bigger picture leads to the conclusion that the greatest contribution to glaucoma in the twentieth century was none of the above.

All of these advances in glaucoma represent technologies, which will one day be replaced by newer and better technologies. What will not be replaced, and what was undoubtedly the most important contribution to glaucoma in the twentieth century, is the knowledge that was gained through scientific investigation, on which all future understanding of the mechanisms of glaucoma and of its management will be based.

At the beginning of the twentieth century, our understanding of the ocular mechanisms related to glaucoma was extremely limited. We knew almost nothing about aqueous humor dynamics; indeed, we did not even know whether aqueous humor was dynamic. We did not know the difference between open-angle and closed-angle glaucoma. We did not know whether elevated intraocular pressure in the various forms of glaucoma was because of reduced outflow or increased inflow. And we knew virtually nothing about the mechanism of glaucomatous optic neuropathy.

During the first half of the twentieth century, there was controversy as to whether aqueous humor was stagnant with general metabolic exchange throughout the ocular tissues or whether there was continuous gross circulation within the anterior ocular segment. It was not until 1941, when Ascher (2) described aqueous veins draining aqueous from the anterior chamber into the venous system, that the theory of continuous circulation was confirmed. Many investigators have subsequently contributed to our current understanding of the anatomy and physiology of aqueous humor production by the ciliary body, the circulation and metabolic activity of aqueous in the anterior ocular segment, and its outflow primarily through the trabecular and uveoscleral pathways.

The mechanisms of the various forms of glaucoma were unknown at the outset of the twentieth century. We did not even know the difference between open-angle and

closed-angle mechanisms of glaucoma, and it was the gonioscopic studies of Barkan

(3) in 1938 that clarified this fundamental classification of the glaucomas and provided a rational basis for their treatment. In 1950, using his concept of tonography to noninvasively estimate the facility of aqueous outflow, Grant (4) showed that in virtually all forms of glaucoma, the mechanism of elevated intraocular pressure is increased resistance to outflow. Many investigators have contributed to our understanding of the specific mechanisms that lead to the increased outflow resistance in the various glaucomas, again providing a more rational approach to management.

Late in the twentieth century, two nascent areas of research were beginning to provide glimpses of what the twenty-first century held in store for the future of glaucoma: the mechanisms of glaucomatous optic neuropathy and the molecular basis of the glaucomas. Several investigators began to disclose pieces of the complex pathways that lead to apoptosis of the retinal ganglion cells in glaucoma, and this information was being applied to the evaluation of pressure-independent neuroprotective agents. Other scientists were reporting preliminary findings in gene-linkage studies for specific forms of glaucoma. These two areas of glaucoma research will likely be the most important as we move farther into the twenty-first century and promise major changes in our understanding and management of glaucoma.

Whatever the future holds for glaucoma research and management, it is clear that the advances will be based on the knowledge that has been gained from the work of basic and clinician scientists over the past decades. The purpose of this book is to review that knowledge. The intent of the book is not primarily to describe the clinical appearances of the glaucomas nor how to manage them. Rather, it is to provide basic scientists, who are working in the field of glaucoma, with a current understanding of the clinical aspects of glaucoma and to provide clinician scientists with the basic knowledge, as they attempt to translate it into rational treatments for glaucoma.

To achieve the goal for this book, we have invited leaders in the various fields to review our current understanding of glaucoma from epidemiology and genetics, through molecular, cellular, and tissue responses, to the mechanisms of the glaucomas and the mechanisms by which we manage them. We are grateful to all the contributors of the book and hope that the contents will be of value to the reader, as we work together to prevent the blindness of glaucoma.

Joyce Tombran-Tink, PhD

Colin J. Barnstable, DPhil

M. Bruce Shields, MD

REFERENCES

1.Goldmann H. Un nouvea tonometer a aplanation. Bull Soc Fr Ophthalmol 1945; 67:474–7.

2.Ascher KW. The Aqueous Veins. Charles C. Thomas, Springfield, IL, 1961.

3.Barkan O. Glaucoma: classification, causes and surgical control. Results of microgonioscopic research. Am J Ophthalmol 1938; 21:1099–17.

4.Grant WM. Tonographic method for measuring the facility and rate of aqueous flow in human eyes. Arch Ophthalmol 1950; 44:204–14.